Ball-milling-mediated remote asymmetric reductive coupling in air

Dicarbofunctionalization reactions of unsaturated systems via radical relay strategies are crucial for the efficient synthesis of complex molecules. Mechanochemical synthesis offers a compelling alternative to traditional solvent-based methods, providing advantages such as straightforward operation, shorter reaction times, minimal solvent use, and simplified workup. Although racemic two- and three-component solid-state cross-coupling reactions have seen significant advancements, the development of their catalytic asymmetric counterparts remains notably limited. In this study, we report a mechanochemical protocol for an asymmetric three-component radical reductive coupling reaction. Leveraging this approach, we successfully synthesized the target products in yields ranging from moderate to excellent (49%-88%) and achieved enantioselectivities of up to 90%. Notably, this is the first reported example of a nickel-catalyzed asymmetric reductive cross-coupling reaction under mechanochemical conditions, thereby expanding the frontiers of asymmetric synthesis within the realm of mechanochemistry.